During the initial funding period, the development of efficient myocardial 3D strain mapping with MR tagging was achieved. The fundamental underpinning of our research is that MRI is the only methodology able to provide high resolution, spatially registered maps of function and perfusion in the intact human. 3D MR strain mapping is also the only non- invasive method capable of unambiguously matching specific coronary territories with truly quantitative parameters of local function. With the advent of effective revascularization techniques and early thrombolysis it has become important to not only detect the presence of coronary artery disease (CAD) prior to the onset of irreversible injury, but also to quantify its functional impact before and after ischemic injury. Thus, in this renewal application, our central objective will remain the characterization of pre- and post-myocardial ischemic injury states. We will continue to explore the potential of 3D tagging but will combine it with perfusion parameters derived from both microsphere and MR perfusion methods. Because clinical relevance of the research is ultimately predicated upon efficient image acquisition and analysis, we will complete the adaptation of our methods to Echo-Planar imaging. Our specific aims will test the following hypotheses: 1) Since coronary perfusion and local function are known to be sensitively coupled prior to ischemic insult, is it possible to accurately quantify the functional reserve of specific myocardial territory using graded levels of pharmacologic stress and repeated 3D measures of strain? Using graded Dobutamine challenges we will establish quantitatively (and, to our knowledge, for the first time) the exact correlation between coronary perfusion reserve and developed local strain in a dog model. We will then test our methods on patients with proven CAD. 2) Accurate characterization of myocardial damage after injury remains a key challenge in the management of the post-infarct patient in whom salvage of the myocardium at risk is a priority. By accurately matching patterns of contrast enhancement and strain maps, is it possible to characterize the true extent of necrotic and salvageable myocardium? Based on promising preliminary results we propose to combine strain and perfusion data in an experimental non-surgical dog model of reperfused infarction to achieve accurate assessment and identification of stunned but salvageable myocardium. We will also continue our clinical exploration of acute reperfused infarction in man with similar methods.